Objective: Little is known about the treatment of psychiatric comorbidities in bipolar disorder. The aim of this review was to summarize the literature on controlled pharmacological trials that have been conducted in psychiatric conditions that commonly co-occur in bipolar disorder. Methods: A Medline search (1980-October 2005) using the terms bipolar disorder and randomized controlled trials, comorbidity, anxiety disorders, alcohol abuse or dependence, substance abuse or dependence, eating disorder, impulse control disorders, attention-deficit disorder, lithium, anticonvulsants, atypical antipsychotic drugs, antidepressants, stimulants was used. Results: The literature establishes a strong association between bipolar disorder and substance abuse/dependence, anxiety disorders, impulse control disorders, eating disorders and attention-deficit hyperactivity disorder. Comorbidity often complicates the diagnosis and the treatment of bipolar disorder and worsens its course of illness and prognosis. Few controlled pharmacological studies have examined the treatment of comorbid conditions in patients with bipolar disorder. Conclusions: Treatment of psychiatric comorbidities in bipolar disorder is not based on controlled data but is largely empirically based. Controlled trials in patients with bipolar disorder and comorbidity are urgently needed.